Dimethylformamide → Methyl 5-chloro-2-cyanobenzoate

HRID 1058274Notes

Reaction equation

HRID 1058274 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:12][C:9]1[CH:10]=[CH:11][C:2]([C:13]#[N:14])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 280500Methyl 2-Bromo-5-chlorobenzoate

Product 1

HCID 12052442Methyl 5-chloro-2-cyanobenzoateYield 88%

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
90 °C

Procedure

To a stirred solution of methyl 2-bromo-5-chlorobenzoate from the previous step (11.5 g, 46 mmol) in degassed DMF (50 mL) was added zinc cyanide (2.82 g, 24.0 mmol) and palladium tetrakis-triphenylphosphine (1.0 g, 0.86 mmol) and the mixture was heated to 90° C. for 18 h. The reaction was partitioned between EtOAc (200 mL) and water (100 mL). The organic phase was concentrated in vacuo and the residue was purified by flash chromatography eluting with a gradient of 10%, 15%, 20% ethyl acetate in hexane yielding methyl 5-chloro-2-cyanobenzoate as a white solid (8.0 g, 88% yield). TLC Rf=0.4 (15% EtOAc-hexanes); HPLC RT=3.13 min, method A; 1H NMR (CDCl3, 400 MHz) 8.13 ppm (d, 1H, J=1.83 Hz); 8.09 ppm (d, 1H, J=8.24 Hz); 7.29 ppm (dd, I H, J=8.34, 2.10 Hz); 4.02 ppm (s, 3H).

Workup

  1. customThe reaction was partitioned between EtOAc (200 mL) and water (100 mL)
  2. concentrationThe organic phase was concentrated in vacuo
  3. customthe residue was purified by flash chromatography
  4. washeluting with a gradient of 10%, 15%, 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-32fd97c6995b4ffe8e487ae0237a381a
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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